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Detection, Diagnosis, and Prognosis of Prostate Cancer

  • Authors: Authors: H. Ballentine Carter, MD; Angelo DeMarzo, MD, PhD; Hans Lilja, MD, PhD
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Target Audience and Goal Statement

This activity is intended for urologists, medical oncologists, radiation oncologists, and other healthcare professionals who treat patients with prostate cancer.

The goal of this activity is to educate physicians regarding the latest research in the diagnosis, treatment, and prevention of prostate cancer.

Upon completion of this activity, participants will be able to:

  1. Describe the controversies surrounding prostate-specific antigen (PSA) measurement in men at risk for prostate cancer.
  2. Identify emerging imaging strategies for the diagnosis of prostate cancer.
  3. Detail the accepted approaches toward staging and grading prostate tumors.
  4. Evaluate emerging factors for risk stratification and outcomes prediction in patients with prostate cancer.


Medscape requires Authors to disclose any relevant financial relationship within the past 12 months with the manufacturer of any product that may relate to the subject matter of the educational activity, whether or not the activity is commercially supported.

Medscape asks Authors to identify, at first mention, investigational products regulated by the US Food and Drug Administration.


  • H. Ballentine Carter, MD

    Professor of Urology and Oncology, Johns Hopkins University School of Medicine; Director, Division of Adult Urology, Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland


    Disclosure: H. Ballentine Carter, MD, has no significant financial interests or relationships to disclose. Dr. Carter may discuss investigational or unlabeled uses of commercial products in this activity.

  • Angelo DeMarzo, MD, PhD

    Associate Professor of Pathology, Oncology, and Urology; Director, Tissue Microarray Core Facility, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland


    Disclosure: Angelo DeMarzo, MD, PhD, has no significant financial interests or relationships to disclose. Dr. DeMarzo may discuss investigational or unlabeled uses of commercial products in this activity.

  • Hans Lilja, MD, PhD

    Attending Research Clinical Chemist, Departments of Clinical Laboratories, Urology, and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY


    Disclosure: Hans Lilja, MD, PhD, has disclosed that he has served as a data evaluator for Ferring Pharmaceuticals, as a consultant or advisor to GenSpera, Inc., and on the prostate cancer steering committee for Sanofi-Synthelabo, and is a patent holder for free PSA assay and hK2 assay. Dr. Lilja may discuss investigational or unlabeled uses of commercial products in this activity.

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    Medscape designates this educational activity for a maximum of 1.25 category 1 credit(s) toward the AMA Physician's Recognition Award. Each physician should claim only those credits that reflect the time he/she actually spent in the activity.

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Detection, Diagnosis, and Prognosis of Prostate Cancer


Assessment: Staging and Grading

The clinical stage of a tumor and its histopathologic grade are established factors used to assess patient risk and prognosis and guide treatment decisions. Although tumor stage and grade have been used alone to predict final pathologic stage and prognosis, when combined with other independent variables in mathematical models, they more accurately predict clinical outcomes.

Clinical Staging Systems

Anatomic-based classification of prostate cancer is described by clinical staging systems, which, together with histopathologic grading, help guide the selection of therapy and assess the risk for disease progression. The two most commonly used staging systems are the tissue, node, and metastasis (TNM) system of the American Joint Committee on Cancer (AJCC) and the Jewett system.

The TNM system classifies tumors according to features of the primary tumor, and assigns tumors to one of four main stages (T1-T4) and several substages (eg, T1c, T2c). This system also assesses the extent of tumor metastasis to regional lymph nodes (N stage) or to metastases beyond (M stage). Like the TNM system, the Jewett staging system assigns tumors into one of four major categories (stages A-D), each of which is associated with substages. According to both of these systems, stages A, B, T1, and T2 refer to clinically localized prostate cancer; stages C, T3, and T4M0 to tumors that have extended beyond the capsule; and stages D and T4M1 to metastatic disease.[8]

Histopathologic Grading

Cancerous tissue from prostate biopsy and prostatectomy specimens is graded histologically, based on the architecture of the glandular tissue, glandular differentiation, and cellular and nuclear appearance; this provides a relative measure of the aggressiveness of the cancer cells.[64,80,81] The most commonly used histopathologic grading system is the Gleason system, which uses a numeric scale to represent the observed histologic patterns. The primary and secondary patterns are each assigned a grade from 1 to 5, which, when added together, yields the Gleason score. This score describes the histologic differentiation of the cancer, and corresponds to broad categories of disease grade: 2-4, well differentiated (very rarely seen on needle biopsy); 5-6, well to moderately differentiated; 7, moderately differentiated; 8-10, poorly differentiated.[8]

Of note, the primary and secondary grades can also contribute prognostic information. For example, patients with 3+4 Gleason score often fare better than patients with 4+3 Gleason score.[8] In one series, patients with Gleason score 4+3 tumors had a significantly greater increased risk of developing metastatic disease compared with patients with Gleason 3+4 tumors, regardless of surgical margins and extent of extraprostatic extension.[82]

Although preoperative Gleason scores in the 2-4 or 8-10 range closely correlate with the final pathologic stage of disease on prostatectomy, there is substantial disparity in Gleason score and final pathologic stage for the 5-7 range -- the range at which most men present clinically.[83] In part, this relates to the sampling problem of prostate needle biopsies mentioned above. While the Gleason score is useful in staging prostate cancer, additional prognostic value may be obtained from the order of the assigned grades (ie, primary and secondary). Therefore, more accurate prediction of the final pathologic stage of a tumor can be made when the Gleason score is combined with information from clinical staging and PSA.[83]